Abstract

BACKGROUND: Thrombocytopenia is a common event in ICU patients, with controversial effects over their outcome. We aimed to assess the importance of thrombocytopenia kinetics on mortality of ICU patients. METHODS: We conducted a retrospective cohort study analyzing patients admitted to the adult ICU from a teaching University Hospital which had at least one platelet count <100,000 cells/mm3. Patients with thrombocytopenia prior to ICU admission were excluded. RESULTS: We analyzed 27 consecutive thrombocytopenic patients admitted to the adult ICU (22.5% of all ICU patients) in a 5-month period. Trauma (40%) and medical illness (26%) were the most common causes of admission. Those who died during ICU stay were significantly older than those who were discharged, and tended to be more severely ill, but there was no difference in bleeding events. The proportion of time with low platelets count in ICU and, specially, thrombocytopenia kinetics (evolution to rising or fall until discharge or death) were related to mortality. CONCLUSION: Thrombocytopenia kinetics, with tendency of declining during length of stay, predicts mortality better than sheer platelet count in ICU patients.

INTRODUCTION

Thrombocytopenia is a common event in ICU patients, with prevalence ranging from 13% to 41% (1-4), and it has meaningful morbidity and economic impact(3).

It may be a multifactorial phenomenon, involving drugs, high consumption and low production of platelets (consumptive coagulopathy and acute illness) and also hemodilution secondary to infusion of fluids and blood products(2). However, the real impact of thrombocytopenia on mortality is debatable, once literature does not clearly show this association(2, 5-8).

Thus, we aimed to determine the relationship between severity of thrombocytopenia andin-hospital/ICU length of stay, as well as assess the relation between the kynetics of thrombocytopenia and morbimortality and describe the clinical and epidemiological profile of patients admitted to the adult ICU of a University Hospital.

METHODS

We conducted a retrospective cohort study through analysis of medical records from patients admitted to the Adult ICU of Western Paraná State University Hospital (a public teaching hospital with 173 beds), in Cascavel (Southern Brazil), for a five-month period who presented with thrombocytopenia. The 14-beds Adult ICU attends post-surgical (emergency and elective procedures), medical, trauma and obstetric patients. Inclusion criteria were: patients admitted to the Adult ICU in the period between August 1stand December 31st, 2011 that presented with thrombocytopenia (detected on one daily exam, at least). Exclusion criteria were: patients with thrombocytopenia prior to ICU admission, even if recorded during-hospital setting.

The data obtained from medical records were tabulated so that differences could be observed in the prognostic role of thrombocytopenia (relation to death in the ICU or hospital). That was done by comparing clinical and epidemiologic factors, such as: gender, age, causes of ICU admission, possible etiologies of thrombocytopenia, and severity of disease at ICU admission (APACHE II score).

Definitions of variables assessed in this paper:

Thrombocytopenia: at least one Platelet count <100,000 cells/mm3.

Major hemorrhage: Bleeding associated with one of the following: a decrease of hemoglobin over 2g/dl or drop of hematocrit over 6%; or need for blood products transfusion; or clinical instability (due to the hemorrhage); or intracranial or gastrointestinal bleeding.

Trauma: Injuries caused by external source; traffic accidents or violence (insults by physical and chemical agents, injury by firearms and bladed weapons, which are common events in Brazilian routine).

Sepsis: it was used definition established by Bone and cols (9).

Leukopenia: at least one blood total leukocyte count <4,000 cells/mm³.

Disseminated intravascular coagulation (DIC): we followed the adapted criteria of Gando and cols (13), using D-dimer as a serum biomarker of fibrinolysis. Whenever platelet count was lower than 80,000 the serum fibrinogen level was measured.

Data were tabulated in Excel® and analyzed with EpiInfo® software. Descriptive statistical analysis was performed, and percentages were compared with chi-square test. Quantitative variables were compared with Student’s t test, analysis of variance and Tukey test, assuming a significance level of p <0.05.

RESULTS

During the study period, 120 patients were admitted to the adult ICU. Of these, 27 presented with thrombocytopenia (22.5%).

Patients were predominantly male (55.5%), young (mean age 43.22 years) and the most common causes of admission were trauma and medical illnesses. Patients who died during ICU stay were significantly older than those who were discharged, and tended to be more severely ill (although no statistically significant difference on APACHE II score was found). Table 1 depicts clinical and epidemiological characteristics of patients at ICU admission.

Table 1

Baseline characteristics of thrombocytopenic ICU patients.

Table 2 exhibits the outcome and bleeding events occurred during ICU stay, with no significant difference between the groups.

Table 2

Thrombocytopenic ICU patients’ outcomes.

Thrombocytopenia kynetics is showed in figures 1 and 2.

Figure 1 compares the amount of time that patients persisted thrombocytopenic throughout ICU stay (relation between thrombocytopenic days and total ICU length of stay). As observed, most of survivors had thrombocytopenia for a time lower than 50% of their stay, whereas non-survivors persisted with low platelet count during hospitalization.

Figure 1

Percent of time patients stayed in ICU with thrombocytopenia (platelet count <100,000/mm³)

Figure 2 displays the evolution of platelet count of both groups, comparing day 1, day 3 and the last day of ICU stay (either the day of discharge or death). There was no significant difference on platelet count between groups up until day 3 of ICU stay. However, from day 3 to the last day in ICU, we registered a significant arise on platelet count of the discharged group.

Figure 2

Platelet count evolution (cell/mm³).

DISCUSSION

We recorded thrombocytopenia in 22.5% of patients admitted to the ICU during the study period. Other studies showed higher overall prevalence of low platelet count (2,3);however, these authors included patients that were already thrombocytopenic at ICU admission as well as those that developed the condition after admission and, also, they considered a higher threshold for thrombocytopenia diagnosis (<150,000 cells/mm³).Our study excluded patients already thrombocytopenic at the time of ICU admission.

Among the causes of hospitalization of patients who developed thrombocytopenia, trauma was the main etiology (40%).Literature reveals that trauma patients have a greater risk to develop thrombocytopenia in ICU. The risk is even higher for older patients, multiple trauma and in more severe cases (10).

In the present study, thrombocytopenic patients had median APACHE II score of 23.0 at ICU admission. This value is considerably higher than those observed by other researchers (ranging from 17.5 to 19.0)(5,7), which means that our patients tended to be more severely ill than those assessed in other studies.It has been shown that patients with APACHE II scores > 22 had higher risk of developing thrombocytopenia (5).

Despite the multifactorial nature of ICU-acquired thrombocytopenia, which includes situations of high consumption and low production of platelets, the clinical setting can provide a series of clues in order to establish the etiology of this event (11). In our study, thrombocytopenia was caused mainly by trauma (44%) and sepsis (15%). When other etiologies could be definitively ruled out and the patient history of heparinuse, we assigned heparin-induced thrombocytopenia (HIT) as cause of low platelet count (11% of patients).

Table 2 shows that there was no significant difference on length of stay between survivors and non-survivors. This could be due to the small size of the sample, or can be due to the great severity of the patients at ICU admission. There was no significant difference between groups regarding the incidence of major bleeding events; hence, thrombocytopenia possibly cannot be pointed as sole cause of hemorrhage in these patients. Jolicoeur and cols(12) reported a 10% occurrence of bleeding events in 1428 ICU patients with platelet counts <120,000 cells/mm³. However, the mortality rate among these thrombocytopenic patients was more strongly related to thromboembolic events than to bleeding itself.

The analysis of Figure 1 shows that survivorshad shorter thrombocytopenic time (around 70% of these individuals were thrombocytopenic for less than 50% of ICU length of stay) comparing to non survivors (50% of these had thrombocytopenia for more than half of ICU time).

Between day 1 and day 3 of ICU stay, platelet count was not significantly different between groups (survivors and non-survivors), unlike what was reported for severely burned patients (13),in which the maintenance of thrombocytopenia between the 1st and 3rd day of admission and/or a drop<50% in platelet count was associated with higher mortality rates.

As seen in Figure 2, the sustained thrombocytopenia was an indicator of higher mortality risk. Among surviving patients, thrombocytopenia was reversed or stabilized until the day of discharge; while in patients who died, platelet count continued to drop throughout ICU stay.

These results allow us to infer that the sheer platelet count had no prognostic relevance; however, the persistence of thrombocytopenic status was a relevant parameter that accompanied a worst outcome of ICU patients.

Some limitations of this study must be pointed out.The retrospective design chosen has some intrinsic limitations related to the reliability of the databases (patients’ records) that can influence the results of data analysis.Another limitation of this study was the absence of serological tests to confirm the HIT (HIT 1 and 2 antibodies). Patients were included in this group when they had a history of heparin use in the absence of any other identifiable causes of thrombocytopenia.Due to the social background of our hospital (few available beds to fulfill the high demand), patients are admitted to the ICU later on the course of their illnesses (average gap of 5.15 days between hospital and ICU admission, even for trauma patients), a factor that can influence the assessment of early clinical events occurring during hospitalization. Thus, the results of this study may not apply to patients admitted to the ICU earlier.

CONCLUSION

In ICU patients, the presence or severity of low platelet counts are not markers of poor prognosis. However, the kinetics of thrombocytopenia (i.e., the tendency of recovery versus persistent low count) strongly correlated with mortality.